Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE(-/-) mice

作者:Mishima Tetsuya; Iwabuchi Kazuya*; Fujii Satoshi; Tanaka Shin Ya; Ogura Hisako; Watano Miyata Keiko; Ishimori Naoki; Andoh Yasuhiro; Nakai Yukihito; Iwabuchi Chikako; Ato Manabu; Kitabatake Akira; Tsutsui Hiroyuki; Onoe Kazunori
来源:International Journal of Molecular Medicine, 2008, 21(2): 181-187.

摘要

Allograft inflammatory factor (AIF)-1, originally cloned from a rat heart allograft under chronic rejection, is induced in various inflammatory conditions including atherosclerosis. Using mouse AIF-1 transfected macrophages and AIF-1 transgenic (AIF-1(Tg)) mice, we analyzed the influence of AIF-1 overexpression on macrophage phagocytosis and the development of atherosclerosis. The AIF-1 transfectants showed significantly increased phagocytosis of latex beads and E. coli BioParticles as well as incorporation of acetylated low-density lipoprotein (LDL) compared to those of vector controls. Concordant results were obtained with elicited peritoneal exudate cells from AIF-1(Tg) mice. When AIF-1(Tg) mice were crossbred with apolipoprotein E knockout mice (ApoE(-/-)), these AIF-1(Tg) ApoE(-/-) mice developed significantly increased atherosclerotic lesions compared to ApoE(-/-) mice. These results suggest that enhanced AIF-1 expression leads to augmented incorporation of degenerated LDL by macrophages and promotes development of atherosclerotic vasculopathy.